PROJECT SUMMARY/ABSTRACT - Overall Breaking down barriers to translational research is the key to finding new approaches to inflammatory arthritis in adults and children. We therefore propose the Joint Biology Consortium (JBC), a shared infrastructure based at the Brigham and Women's Hospital, Boston Children's Hospital, and the Broad Institute to accelerate the work of an arthritis-focused Research Community at 17 research centers in the US and abroad. Three Cores designed around the shared needs of JBC members will enhance the efficiency of existing studies, facilitate innovation, and foster junior investigators. 1. The Administrative Core is the organizational heart of the JBC, coordinating operations and cultivating the scientific potential of the JBC research network. The JBC Synergy Meeting promotes scientific interchange and collaboration, while the JBC Web Portal facilitates communication and service delivery. The JBC Enrichment Program, incorporating innovations from award-winning mentors, supports JBC Young Investigators via grant aims review, a novel mentoring program, and microgrants to enable utilization of JBC core service. 2. The Human Biosamples Core provides ?one stop shopping? for adult and pediatric biospecimens essential to arthritis research. Web-based searches and targeted in-clinic recruitment will transform multiple distinct resources at BWH and Children's into a unified pipeline for biospecimens and associated clinical and genetic data. 3. The Cellular Systems Core provides resource- and expertise-intensive tools for arthritis research. Key services include centralized human sample processing, CyTOF, single-cell and low-input RNA-seq, and an innovative HoxB8 technology core for generation and CRISPR/Cas9 manipulation of pre-clinical model cells, including neutrophils, monocytes, and osteoclasts. Spearheaded by committed arthritis researchers Director Dr. Peter Nigrovic and Associate Director Dr. Elizabeth Karlson, the JBC will spur innovation within an inclusive and highly collaborative network of senior and junior investigators, leading the Joint Biology Consortium to become an engine of translational research in adult and pediatric arthritis.